Researchers, alternative health enthusiasts, and the pharmaceutical industry are interested in lithium’s pro-cognitive potential
STUDY: Moore GJ et al, JAMA Psychiatry 2026
STUDY TYPE: Narrative review
FUNDING: Independent
Background
After 75 years of use in bipolar disorder, researchers are considering whether lithium’s brain-protecting effects can extend to dementia. Those mechanisms involve:
- Bcl-2, which prevents neuronal death
- Brain-derived neurotrophic factor (BDNF), involved in neuronal growth and protection
- GSK-3 beta, and enzyme involved in dementia-related tau tangles, amyloid production, and preservation of brain neurons and their energy source (mitochondrial)
This narrative review from JAMA Psychiatry pulls together preclinical models, human neuroimaging, large registry studies, and a handful of early randomized trials in patients with amnestic mild cognitive impairment or early Alzheimer disease.
Summary
In humans, brain imaging links lithium exposure to more N-acetylaspartate, a marker of neuron health, and to preserved or increased gray matter in regions that typically atrophy in Alzheimer disease.
A large Danish registry study linked lithium exposure to lower dementia incidence, with longer exposure linked to greater protection, though it was not randomized so confounding can’t be ruled out.
Small, randomized trials of low-dose lithium in older adults with mild cognitive impairment found slower cognitive decline and favorable cerebrospinal fluid tau changes over one to three years. The problem is the samples were small, and a negative study raises doubts. The 2-year LATTICE study missed its primary endpoint but slowed verbal memory decline. Some believe the negative finding was due to using lithium carbonate instead of orotate, but that has yet to tested in humans.
Amyloid plaques may act as a lithium sink, depleting lithium in vulnerable regions, a problem orotate may overcome. Lithium orotate is now being explored because it may resist this sequestration and reach the brain at lower, kidney- and thyroid-sparing doses than lithium carbonate.
Practice Implications
- I’ll curb my enthusiasm while awaiting clearer results.
- Those are likely to come, as the pharmaceutical industry is testing a branded version of lithium in dementia.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
